Antisense oligonucleotides are accepted therapeutic modalities and many thousands of patients have been treated with antisense compounds. The original “first generation” antisense compounds employed in the first antisense clinical trials were oligodeoxynucleotides having 2′-deoxy ribonucleotides and phosphorothioate internucleoside linkages. Subsequently, chimeric “second generation” antisense oligonucleotides exhibited a marked improvement in potency over first generation antisense oligonucleotides. Second generation antisense oligonucleotides are chimeric oligonucleotides typically having a 2′-deoxy “gap” region flanked by “wings” having nucleotides with 2′-modified ribonucleotides, referred to as “gapmers.” The most widely used of the “second generation” antisense motifs is often referred to as a “MOE gapmer” in which the 2′-modified ribonucleotide is a 2′-O-methoxyethyl (2′-MOE or simply MOE) modification, and each of the internucleotide linkages is a phosphorothioate. Predominantly, second generation oligonucleotides have a length of 20 nucleotides of which the 5 nucleotides at each terminus are 2′-MOE nucleotides and the center ten nucleotides are 2′-deoxyribonucleotides. These second generation oligonucleotides are referred to as “5-10-5 MOE gapmers” have a 5-10-5 wing-gap-wing motif. Chimeric antisense compounds with other arrangements of modifications have also been made. “Hemimers,” are chimeric compounds in which there is a single 2′-modified “wing” adjacent to (on either the 5′, or the 3′ side of) a 2′-deoxy gap have been described (Geary et al., 2001, J. Pharm. Exp. Therap., 296, 898-904).